The important contribution of computed tomography (CT) to modern medicine is readily apparent. Recently, the issue of the radiation dose related to body CT has received considerable attention, in part because of its success and high rate of clinical utilization. Because the absence of a non-zero risk related to the current levels of radiation exposures from CT cannot be conclusively proven, there is a dire need for more robust dose reduction strategies at body CT. This, however, must be implemented without a significant compromise in diagnostic accuracy. The overarching objective of the proposal is to develop, optimize, and evaluate an iterative image reconstruction algorithm that holds a promise to reduce radiation dose by 70%-90% from current levels, without compromising diagnostic accuracy. By employing the proposed DR-PICCS reconstruction, sub-mSv abdominal CT scanning with preserved diagnostic accuracy may be achievable for a number of clinical applications, such as evaluation for urolithiasis and colorectal polyps. For other diagnostic imaging applications, dose reductions on the order of 70%-90% may be possible, again with preserved diagnostic performance. Preliminary results from our retrospective and prospective pilot studies have demonstrated the feasibility of the proposed study by our collaborative translational research group. The following specific aims will be carried out to accomplish our proposed overall objective: (1) Optimization of the DR-PICCS implementation for ultra-low-dose abdominal CT imaging; (2) Prospective validation of ultra-low- dose diagnostic abdominal CT images reconstructed with DR-PICCS reconstruction algorithm. This aim includes demonstration of equivalence in image noise and diagnostic accuracy between ultra-low-dose DR- PICCS reconstructions and current standard-of-care dose FBP images; and performance comparison of ultra- low-dose CT with DR-PICCS against other commercially-available reconstruction techniques; and (3) Prospective validation of sub-mSv CT imaging for virtual colonoscopy (CT colonography) screening. Successful completion of this project will provide valuable information about the clinical feasibility and utility of ultra-low-dose abdominal CT imaging, including optimization of a practical technique (Aim 1), validation of diagnostic accuracy (Aim 2), and application to colorectal cancer screening (Aim 3). The successful completion of the project will also provide a methodological paradigm and unique CT data sets needed to clinically evaluate other ultra-low-dose CT imaging reconstruction methods.